CHD8 p.Pro2080=
c.6240A>G · rs2501855642 · VCV1703105
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 6.21e-05%)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.011 | GERP -0.053, phastCons 0.95 |
| Overall | ||
| CADD | 8.699 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.21e-05%
Overall
6.21e-05%
1/1,610,256 alleles · very rare
exomes 1/1,457,980 · genomes 0/152,276 · joint denominator
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- CHD8
- Protein
- p.Pro2080=
- Coding
- c.6240A>G
- MANE Select
- NM_001170629
- dbSNP
- rs2501855642
- Type
- single nucleotide variant
- Location
- chr14:21393555 (GRCh38)
- Gene constraint
- LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 55.17 · 2 PDB
- Residue 2080
- the 'interaction with fam124b' region; the 'disordered' region
Similar variants
- CHD8 c.3882+1G>A Pathogenic/Likely pathogenic ★★ same type
- CHD8 p.Arg1188Ter Pathogenic ★★ same type
- CHD8 p.Arg1242Gln Likely pathogenic ★★ same type
- CHD8 p.Arg1242Ter Pathogenic ★★ same type
- CHD8 p.Arg1245Ter Pathogenic ★★ same type
- CHD8 p.Arg1337Ter Pathogenic ★★ same type
- CHD8 p.Arg1402Ter Pathogenic/Likely pathogenic ★★ same type
- CHD8 p.Arg1460Ter Pathogenic ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/chd8-p-pro2080 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown